Spinal implant system and method

ABSTRACT

A delivery system comprising an agent and a foldable covering including a first surface disposed with the agent and a second surface connectable with the first surface to intra-operatively dispose the covering in a selected configuration.

FIELD

The present disclosure generally relates to medical devices for thetreatment of musculoskeletal disorders, and more particularly to aspinal implant system and a method for treating a spine.

BACKGROUND

Spinal pathologies and disorders such as degenerative disc disease, discherniation, spondylolisthesis, stenosis, osteoporosis, tumor, scoliosisand other curvature abnormalities, kyphosis and fracture may result fromfactors including trauma, disease and degenerative conditions caused byinjury and aging. Spinal disorders typically result in symptomsincluding deformity, pain, nerve damage, and partial or complete loss ofmobility.

Non-surgical treatments, such as medication, rehabilitation and exercisecan be effective, however, may fail to relieve the symptoms associatedwith these disorders. Surgical treatment of these spinal disordersincludes fusion, fixation, correction, discectomy, microdiscectomy,corpectomy, decompression, laminectomy, laminotomy, foraminotomy,facetectomy and implantable prosthetics. As part of these surgicaltreatments, spinal constructs including implants, such as, for example,bone graft, bone fasteners, spinal rods and interbody devices can beused to provide stability to a treated region. For example, duringsurgical treatment, surgical instruments can be used to delivercomponents of the spinal constructs to the surgical site for fixationwith bone to immobilize a joint. This disclosure describes animprovement over these prior technologies.

SUMMARY

In one embodiment, a spinal implant is provided. The spinal implant hasan agent and a foldable covering including a first surface disposed withthe agent and a second surface connectable with the first surface tointra-operatively dispose the covering in a selected configuration.

BRIEF DESCRIPTION OF THE DRAWINGS

The present disclosure will become more readily apparent from thespecific description accompanied by the following drawings, in which:

FIG. 1 is a perspective view of components of one embodiment of a systemin accordance with the principles of the present disclosure;

FIG. 2 is a perspective view of the components shown in FIG. 1;

FIG. 3 is a perspective view of the components shown in FIG. 1;

FIG. 4 is a perspective view of the components shown in FIG. 1; and

FIG. 5 is a perspective view of components of one embodiment of a systemin accordance with the principles of the present disclosure disposedwith vertebrae.

DETAILED DESCRIPTION

The exemplary embodiments of a spinal implant system are discussed interms of medical devices for the treatment of musculoskeletal disordersand more particularly, in terms of a spinal implant system for treatinga spine at a surgical site and a method for treating a spine. In someembodiments, the present system comprises a spinal implant that deliversa substance to the surgical site. In some embodiments, the presentsystem comprises a spinal implant employed with a spinal joint andfusion, for example, with a cervical, thoracic, lumbar and/or sacralregion of a spine.

In some embodiments, the spinal implant system includes autologous bone,either from the iliac crest or local bone from decompressions. In someembodiments, the spinal implant system includes retention of autologousbone at the site of implantation. In some embodiments, the spinalimplant includes a resorbable porous mesh sheet that incorporates a hookand loop fastener. In some embodiments, the mesh sheet is configured toadhere to itself when folded. In some embodiments, the spinal implantincludes a sheet combined with autograft and configured to be foldedinto a selected implant configuration intra-operatively. In someembodiments, the spinal implant system provides for customization of thespinal implant to meet surgical and/patient needs.

In some embodiments, the spinal implant includes a resorbable porouspolymer mesh sheet with hooks on one surface that adhere to the oppositesurface of the mesh when the surfaces are folded together. In someembodiments, the spinal implant system includes a spinal implantconfigured for intra-operative folding into a selected implantconfiguration to deliver and retain autograft at the site ofimplantation. In some embodiments, the spinal implant system includesfull intra-operative customization of a selected implant configurationto a desired shape and/or volume required.

In some embodiments, the system of the present disclosure may beemployed to treat spinal disorders such as, for example, degenerativedisc disease, disc herniation, osteoporosis, spondylolisthesis,stenosis, scoliosis and other curvature abnormalities, kyphosis, tumorand fractures. In some embodiments, the system of the present disclosuremay be employed with other osteal and bone related applications,including those associated with diagnostics and therapeutics. In someembodiments, the disclosed system may be alternatively employed in asurgical treatment with a patient in a prone or supine position, and/oremploy various surgical approaches to the spine, including anterior,posterior, posterior mid-line, direct lateral, postero-lateral, and/orantero-lateral approaches, and in other body regions. The system of thepresent disclosure may also be alternatively employed with proceduresfor treating the lumbar, cervical, thoracic, sacral and pelvic regionsof a spinal column. The system of the present disclosure may also beused on animals, bone models and other non-living substrates, such as,for example, in training, testing and demonstration.

The system of the present disclosure may be understood more readily byreference to the following detailed description of the embodiments takenin connection with the accompanying drawing figures, which form a partof this disclosure. It is to be understood that this application is notlimited to the specific devices, methods, conditions or parametersdescribed and/or shown herein, and that the terminology used herein isfor the purpose of describing particular embodiments by way of exampleonly and is not intended to be limiting. In some embodiments, as used inthe specification and including the appended claims, the singular forms“a,” “an,” and “the” include the plural, and reference to a particularnumerical value includes at least that particular value, unless thecontext clearly dictates otherwise. Ranges may be expressed herein asfrom “about” or “approximately” one particular value and/or to “about”or “approximately” another particular value. When such a range isexpressed, another embodiment includes from the one particular valueand/or to the other particular value. Similarly, when values areexpressed as approximations, by use of the antecedent “about,” it willbe understood that the particular value forms another embodiment. It isalso understood that all spatial references, such as, for example,horizontal, vertical, top, upper, lower, bottom, left and right, are forillustrative purposes only and can be varied within the scope of thedisclosure. For example, the references “upper” and “lower” are relativeand used only in the context to the other, and are not necessarily“superior” and “inferior”.

As used in the specification and including the appended claims,“treating” or “treatment” of a disease or condition refers to performinga procedure that may include administering one or more drugs to apatient (human, normal or otherwise or other mammal), employingimplantable devices, and/or employing instruments that treat thedisease, such as, for example, microdiscectomy instruments used toremove portions bulging or herniated discs and/or bone spurs, in aneffort to alleviate signs or symptoms of the disease or condition.Alleviation can occur prior to signs or symptoms of the disease orcondition appearing, as well as after their appearance. Thus, treatingor treatment includes preventing or prevention of disease or undesirablecondition (e.g., preventing the disease from occurring in a patient, whomay be predisposed to the disease but has not yet been diagnosed ashaving it). In addition, treating or treatment does not require completealleviation of signs or symptoms, does not require a cure, andspecifically includes procedures that have only a marginal effect on thepatient. Treatment can include inhibiting the disease, e.g., arrestingits development, or relieving the disease, e.g., causing regression ofthe disease. For example, treatment can include reducing acute orchronic inflammation; alleviating pain and mitigating and inducingre-growth of new ligament, bone and other tissues; as an adjunct insurgery; and/or any repair procedure. Also, as used in the specificationand including the appended claims, the term “tissue” includes softtissue, ligaments, tendons, cartilage and/or bone unless specificallyreferred to otherwise. The term bone, as used herein, refers to bonethat is cortical, cancellous or cortico-cancellous of autogenous,allogenic, xenogenic, or transgenic origin unless specifically referredto otherwise.

Notwithstanding the numerical ranges and parameters set forth herein,the broad scope of this disclosure are approximations, the numericalvalues set forth in the specific examples are reported as precisely aspossible. Any numerical value, however, inherently contains certainerrors necessarily resulting from the standard deviation found in theirrespective testing measurements. Moreover, all ranges disclosed hereinare to be understood to encompass any and all subranges subsumedtherein. For example, a range of “1 to 10” includes any and allsubranges between (and including) the minimum value of 1 and the maximumvalue of 10, that is, any and all subranges having a minimum value ofequal to or greater than 1 and a maximum value of equal to or less than10, e.g., 5.5 to 10.

Demineralized, as used herein, refers to any material generated byremoving mineral material from tissue, for example, bone tissue. Incertain embodiments, the demineralized compositions described hereininclude preparations containing less than 5% calcium and preferably lessthan 1% calcium by weight. Partially demineralized bone (e.g.,preparations with greater than 5% calcium by weight but containing lessthan 100% of the original starting amount of calcium) is also consideredwithin the scope of this disclosure. In some embodiments, demineralizedbone has less than 95% of its original mineral content. Demineralized isintended to encompass such expressions as “substantially demineralized,”“partially demineralized,” and “fully demineralized.”

Demineralized bone matrix, as used herein, refers to any materialgenerated by removing mineral material from bone tissue. In preferredembodiments, the DBM compositions as used herein include preparationscontaining less than 5% calcium and preferably less than 1% calcium byweight. Partially demineralized bone (e.g., preparations with greaterthan 5% calcium by weight but containing less than 100% of the originalstarting amount of calcium) are also considered within the scope of thisdisclosure.

Osteoconductive, as used herein, refers to the ability of anon-osteoinductive substance to serve as a suitable template orsubstance along which bone may grow.

Osteogenic, as used herein, refers to the ability of an agent, material,or implant to enhance or accelerate the growth of new bone tissue by oneor more mechanisms such as osteogenesis, osteoconduction, and/orosteoinduction.

Osteoimplant, as used herein, refers to any bone-derived implantprepared in accordance with the embodiments of this disclosure andtherefore is intended to include expressions such as bone membrane, bonegraft, etc.

Osteoinductive, as used herein, refers to the quality of being able torecruit cells from the host that have the potential to stimulate newbone formation. Any material that can induce the formation of ectopicbone in the soft tissue of an animal is considered osteoinductive. Forexample, most osteoinductive materials induce bone formation in athymicrats when assayed according to the method of Edwards et al.,“Osteoinduction of Human Demineralized Bone: Characterization in a RatModel,” Clinical Orthopaedics & Rel. Res., 357:219-228, December 1998,incorporated herein by reference.

Superficially demineralized, as used herein, refers to bone-derivedelements possessing at least about 90 weight percent of their originalinorganic mineral content, the expression “partially demineralized” asused herein refers to bone-derived elements possessing from about 8 toabout 90 weight percent of their original inorganic mineral content andthe expression “fully demineralized” as used herein refers to bonecontaining less than 8% of its original mineral context.

In various embodiments, the spinal implant comprisespoly(lactide-co-glycolide) (PLGA), polylactide (PLA), polyglycolide(PGA), D-lactide, D,L-lactide, L-lactide, D,L-lactide-co-ε-caprolactone,D,L-lactide-co-glycolide-co-ε-caprolactone, L-lactide-co-ε-caprolactoneor a combination thereof.

In one embodiment, as shown in FIGS. 1-4, an osteogenic spinal implantsystem 10, similar to the systems, constructs, implants and methodsdescribed herein and including the components discussed, comprises aspinal implant 11. Spinal implant 11 includes a foldable coveringincluding a plurality of foldable walls and an agent. The coveringincludes a first configuration, such as, for example, a flatconfiguration, as shown in FIG. 1, and is manipulated and/or folded, asshown in FIGS. 2-4, into a selected implant configurationintra-operatively, as shown in FIG. 5.

In some embodiments, the covering may be a temporary covering whereinthe covering is substantially resorbable. For example, the covering maybe formed of a material that is substantially resorbed within 2 weeks,within 4 weeks, within 12 weeks, or within other suitable time frame. Insome embodiments, FIGS. 1-4, an osteogenic spinal implant system 10including the covering may be a temporary delivery system. In someembodiments, the covering may include one or more attachment mechanismsfor retaining spinal implant 11 at the surgical site. The attachmentmechanism may be a mechanical attachment mechanism, a physicalattachment mechanism, a biological attachment mechanism or a chemicalattachment mechanism, or may employ combinations of these. Theattachment mechanism may be used to attach the covering to skeletal orsoft tissue proximate the surgical site.

In some embodiments, the covering may be used for containment ofparticulate or morselized materials, optionally to provide a focus orconcentration of biological activity. In some embodiments, the coveringmay be used for containment of a substance one or more of boneparticles, bone fibers, other osteoinductive or osteoconductivematerials, BMP, antibiotics, or other materials.

In some embodiments, the covering may be used for maintaining materialsin spatial proximity to one another, possibly to provide a synergisticeffect. In some embodiments, the covering may be used to controlavailability of an agent provided within the covering to cells andtissues of a surgical site over time.

In some embodiments, the covering may contain an agent such as a graftmaterial. The covering limits, and in some embodiments eliminates, graftmigration and maintains graft density. Spinal implant 11 including theagent may be configured to conform to surrounding bony contours orimplant space. In some embodiments, spinal implant 11 provides a pathwayfor healing/cell penetration and tissue ingrowth. Thus, the covering mayfacilitate transfer or diffusion of materials into and out of thecovering. For example, the covering may facilitate diffusion from thecovering of an agent provided within the covering or may facilitatediffusion into the covering of materials at the surgical site, such ascells and tissues, into the covering. The covering may be configured topermit diffusion of some agent/materials while substantially preventingdiffusion of other agent/materials. Further, in some embodiments, thecovering may be configured such that diffusion is permitted into or outof certain portions of the covering but not other portions of thecovering.

In some embodiments, the covering may comprise a structural materialand, in some embodiments, a functional material. The structural materialmay comprise a mesh material or a polymeric material. The functionalmaterial may comprise, for example, a radiopaque material or abacteriocidal material. In some embodiments, the covering may beflexible, non-elastic, or elastic. The covering material may be braided,woven, non-woven shape memory, particulate, threaded, porous,non-porous, or substantially solid.

In some embodiments, the covering may participate in, control,facilitate, prevent, or otherwise adjust the release of an agent. Forexample, the covering may act as a selectively permeable membrane and/ormay be porous, with the level of porosity being related to the nature ofthe agent inside the covering. Thus, the material and configuration ofthe covering may be selected or adjusted based on desired releasecharacteristics. Specific properties of the structural material that maybe adjusted include thickness, permeability, porosity, strength,flexibility, and/or elasticity. In some embodiments, the thickness andporosity of the material may contribute to its strength, flexibility,and elasticity. In some embodiments, the covering may be made of asquishy, moldable, sticky, and/or tacky material to facilitate placementand packing of the covering.

In some embodiments, the covering may be porous to fluid and/or cells,may be biocompatible, and may be resistant to rupture. In someembodiments, the covering may be load-bearing. The covering may beresorbable or non-resorbable. The covering may provide increasedhandling properties, may have irrigation resistance, may have materialretention characteristics, and/or may support cellular penetration. Ifthe covering is made from a resorbable material, the covering degradesand disappears after a period of time. The covering thus may beconsidered a temporary covering. If the covering is not made of aresorbable material, the covering remains in the body. Tissue ingrowthmay occur to bind the host tissue to the agent provided within thecovering. Tissue ingrowth through and around the covering, between thehost tissue and the agent provided within the covering, may be promotedvia openings in the covering.

In some embodiments, the covering may comprise a porous material or amesh material. The size of the pores of the covering may be designed topermit cellular infiltration (approximately several microns to severalmillimeters), but may also be designed specifically to exclude cellsfrom the inside of the covering (for example, approximately 0.45microns) and only allow diffusion of small molecules (proteins andhormones). Thus, the covering may act to control access to the interiorof the delivery system by cells. U.S. Patent Application Publication No.2005/0283255 for Tissue-Derived Mesh for Orthopedic Regenerationdescribes suitable manners for forming a mesh for use with a covering asprovided herein and is herein incorporated by reference in its entirety.

In some embodiments, the covering may include one or more layers, and/orone or more separate sections or compartments. For example, in anembodiment comprising two compartments, one or more agents may be usedfor the first compartment and a different agent or agents may be usedfor the second compartment. For example, one compartment or portionsthereof may be made of an agent or agents that provide a desiredproperty or properties relative to other compartments or portionsthereof, such as increased or decreased resorbability or stiffness, orthe different compartments or portions thereof may be imparted withdifferent drug delivery properties. Alternatively, all compartments maycomprise the same agent or mixtures of agents. Where the characteristicsof the material are varied between compartments or over the surface of asingle compartment, the pores of the first compartment or portionthereof may be larger than the pores of the second compartment. In someembodiments, the covering comprises two compartments, first and secondagents may be used for the first and second compartments, respectively.The first agent may release or expose a growth factor according to afirst rate and the second agent may release a growth factor according toa second rate. Further, the growth factors released by the first andsecond compartments may be the same or may be different. For example, anangiogenic growth factor may be provided with the first compartment andan osteoinductive growth factor may be provided with the secondcompartment.

In embodiments comprising more than one compartment, characteristics ofthe covering material may be varied between compartments. Generally, theporosity, flexibility, strength, or any other characteristic of onecompartment may vary from that characteristic of the other compartment.Further, characteristics of the covering may vary at different positionsof the covering regardless of compartmental configuration of thecovering.

The covering may be configured for specific compressive strength andrigidity by adjusting density and resorption time of the covering. Insome embodiments, a coating may be provided over the covering. Forexample, the coating may be a compound of poly-L-lactide, ofpolyglycolic acid, or their polymers, or polyhydroxyalkanoates(polyhydroxybutyrates and polyhydroxyvalerates and copolymers). Thecoating may be selected such that it has a resorption time wherein it isresorbed by the body and the agent within the covering is permitted toexit through openings in the covering.

In some embodiments, the covering may be fabricated from a polymericmaterial (for example, see U.S. Pat. Nos. 6,696,073, 6,478,825,6,440,444, and 6,294,187, 7,985,414 and U.S. Patent Publication No. and2005/0251267, all herein incorporated by reference in their entirety);woven material and braided material (for example, see U.S. PatentPublication No. 2005/0283255, herein incorporated by reference in itsentirety); non-woven materials; shape memory material; porous materials;and non-porous materials may be used. In some embodiments, outerparticles may be used to contain inner particles; particles may beattached to threads of material, and/or porosity may be added to meshfibers. In some embodiments, materials may be used for portions of thecovering, such as for a compartment of the covering, that aresubstantially impenetrable.

In some embodiments, the covering may be formed of a polymer (such aspolyalkylenes, for example, polyethylenes, polypropylenes), polyamides,polyesters, poly(glaxanone), poly(orthoesters), poly(pyrolicacid),poly(phosphazenes), polycarbonate, other bioabsorbable polymer such asDacron or other known surgical plastics, a natural biologically derivedmaterial such as collagen, gelatin, chitosan, alginate, a ceramic (withbone-growth enhancers, hydroxyapatite), PEEK (polyether-etherketone),dessicated biodegradable material, metal, composite materials, abiocompatible textile (for example, cotton, silk, linen), extracellularmatrix components, tissues, or composites of synthetic and naturalmaterials, or other. Various collagen materials can be used, alone or incombination with other materials, including collagen sutures andthreads. Some examples include polymer or collagen threads woven, orknitted, into a mesh. Other suitable materials include thin polymersheets molded in the presence of a porogen and having underwentleaching; polymer sheets or naturally derived sheets such as fascia andother collagen materials, small intestinal submucosa, or urinary bladderepithelium, the sheets being punctured to introduce porosity; specificshapes printed using available or future printing technologies;naturally secreted materials such as bacterial cellulose grown withinspecific molds.

In some embodiments, the covering may be formed as a sheet, as a mesh,or in other configurations. In some embodiments, the covering may be atextile type material. Thus, for example, the covering may be formedusing a textile approach such as be weaving, rug making, knitting. Suchformation may be by a mechanical or industrial method. In anotherembodiment, a substantially solid sheet may be formed and may be treatedto assume a selected implant configuration penetrable by cells, fluids,and proteins. For example, the sheet may be perforated and expand tocreate openings. In some embodiments, the covering may include a thinsheet that is perforated, expanded to create openings, or otherwise makeit penetrable by cells, fluids and proteins in a selected implantconfiguration.

The foldable covering includes a polymer mesh sheet 12, which has aplurality of foldable walls that include a side 14 and a side 22. Insome embodiments, the covering may comprise a mesh material, such as,for example, natural materials, synthetic polymeric resorbablematerials, synthetic polymeric non-resorbable materials, and othermaterials. Natural mesh materials include silk, extracellular matrix(such as DBM, collagen, ligament, tendon tissue, or other),silk-elastin, elastin, collagen, and cellulose. Synthetic polymericresorbable materials include poly(lactic acid) (PLA), poly(glycolicacid) (PGA), poly(lactic acid-glycolic acid) (PLGA), polydioxanone, PVA,polyurethanes, polycarbonates, polyhydroxyalkanoates(polyhydroxybutyrates and polyhydroxyvalerates and copolymers),polysaccharides, polyhydroxyalkanoates polyglycolide-co-caprolactone,polyethylene oxide, polypropylene oxide, polyglycolide-co-trimethylenecarbonate, poly(lactic-co-glycolic acid), and others. See Chen and Wu,“The Application of Tissue Engineering Materials,” Biomaterials, 2005,26(33): p. 6565-78, herein incorporated by reference in its entirety.Other suitable materials include carbon fiber, metal fiber,polyertheretherketones, non-resorbable polyurethanes, polyethers of alltypes, polyethylene terephthalate, polyethylene, polypropylene, Teflon,and various other meshes. In some embodiments, the covering may comprisenon-woven material such as spun cocoon or shape memory materials havinga coil shape or shape memory alloys.

In some embodiments, mesh fibers may be treated to impart porosity tothe fibers. This may be done, for example, to PLA, PLGA, PGA, and otherfibers. One suitable method for treating the mesh fibers comprisessupercritical carbon dioxide treatment to partially solubilize theparticles. This treatment may further be carried out for viralinactivation. Another suitable method for treating the mesh fiberscomprises explosive decompression. Explosive decompression generatesporosity and leads to controlled permeability. The mesh material furthermay be loaded with cells, growth factors, or bioactive agents.

In some embodiments, fibers of a mesh material may be treated such as byhaving particles adhered thereto. The particles may be, for example,bone particles. Thus, in one embodiment, the covering may comprise aplurality of threads formed into a fabric. The threads may haveparticles adhered thereto. For example, the threads may have particlesstrung on the thread. In an alternative embodiment, the covering may beformed of a material and the material may be coated with particles.

Side 14 includes a surface 16, which is configured to receive an agent20, as described herein. In some embodiments, the agent can includeautograft or allograft.

In some embodiments, the agent that is placed in the device can bedemineralized bone material (e.g., fibers, chips, powder, or acombination thereof). In some embodiments, the demineralized bone fiberscan be elongated and have an aspect ratio of at least from about 50:1 toabout at least about 1000:1. Such elongated bone fibers can be readilyobtained by any one of several methods, for example, by milling orshaving the surface of an entire bone or relatively large section ofbone.

In other embodiments, the length of the fibers can be at least about 3.5cm and average width from about 20 mm to about 1 cm. In variousembodiments, the average length of the elongated fibers can be fromabout 3.5 cm to about 6.0 cm and the average width from about 20 mm toabout 1 cm. In other embodiments, the elongated fibers can have anaverage length be from about 4.0 cm to about 6.0 cm and an average widthfrom about 20 mm to about 1 cm.

In yet other embodiments, the diameter or average width of the elongatedfibers is, for example, not more than about 1.00 cm, not more than 0.5cm or not more than about 0.01 cm. In still other embodiments, thediameter or average width of the fibers can be from about 0.01 cm toabout 0.4 cm or from about 0.02 cm to about 0.3 cm.

In another embodiment, the aspect ratio of the fibers can be from about50:1 to about 950:1, from about 50:1 to about 750:1, from about 50:1 toabout 500:1, from about 50:1 to about 250:1; or from about 50:1 to about100:1. Fibers according to this disclosure can advantageously have anaspect ratio from about 50:1 to about 1000:1, from about 50:1 to about950:1, from about 50:1 to about 750:1, from about 50:1 to about 600:1,from about 50:1 to about 350:1, from about 50:1 to about 200:1, fromabout 50:1 to about 100:1, or from about 50:1 to about 75:1.

In some embodiments, the bone chips can be used and they can be combinedwith bone fibers, where the chips to fibers ratio is about 90:10, 80:20,70:30, 60:40, 50:50, 40:60, 30:70, 20:80 and/or 10:90. In variousembodiments, a surface demineralized bone chips to fibers ratio is about90:10, 80:20, 70:30, 60:40, 50:50, 40:60, 30:70, 20:80 and/or 10:90 thatcan be used in the device. In some embodiments, a surface demineralizedchips to fully demineralized fibers ratio is about 90:10, 80:20, 70:30,60:40, 50:50, 40:60, 30:70, 20:80 and/or 10:90 that can be used in thedevice.

In some embodiments, the agent can include protein, bone morphogeneticproteins, carbohydrate, lipids, collagen, allograft bone, autograftbone, tricalcium phosphate, hydroxyapatite, growth and differentiationfactors, carriers for growth factors, growth factors extracts of tissue,bone marrow aspirate, concentrates of lipid derived or marrow derivedadult stem cells, umbilical cord derived stem cells, committed orpartially committed cells from osteogenic or chondrogenic lineage,antimicrobials, antibiotics, or combinations thereof.

In some embodiments, the agent includes a bioactive agent or bioactivecompound, which includes a compound or entity that alters, inhibits,activates, or otherwise affects biological or chemical events. Forexample, bioactive agents may include, but are not limited to,osteogenic or chondrogenic proteins or peptides, anti-AIDS substances,anti-cancer substances, antibiotics, immunosuppressants, anti-viralsubstances, enzyme inhibitors, hormones, neurotoxins, opioids,hypnotics, anti-histamines, lubricants, tranquilizers, anti-convulsants,muscle relaxants and anti-Parkinson substances, anti-spasmodics andmuscle contractants including channel blockers, miotics andanti-cholinergics, anti-glaucoma compounds, anti-parasite and/oranti-protozoal compounds, modulators of cell-extracellular matrixinteractions including cell growth inhibitors and antiadhesionmolecules, vasodilating agents, inhibitors of DNA, RNA or proteinsynthesis, anti-hypertensives, analgesics, anti-pyretics, steroidal andnon-steroidal anti-inflammatory agents, anti-angiogenic factors,angiogenic factors, anti-secretory factors, anticoagulants and/orantithrombotic agents, local anesthetics, ophthalmics, prostaglandins,anti-depressants, anti-psychotic substances, anti-emetics, and imagingagents. In certain embodiments, the bioactive agent is a drug. In someembodiments, the bioactive agent is a growth factor, cytokine,extracellular matrix molecule or a fragment or derivative thereof, forexample, a cell attachment sequence such as RGD. A listing of bioactiveagents and specific drugs suitable for use with the present disclosuremay be found in “Pharmaceutical Substances: Syntheses, Patents,Applications” by Axel Kleemann and Jurgen Engel, Thieme MedicalPublishing, 1999; the “Merck Index: An Encyclopedia of Chemicals, Drugs,and Biologicals”, Edited by Susan Budavari et al., CRC Press, 1996; andthe United States Pharmacopeia-25/National Formulary-20, published bythe United States Pharmcopeia Convention, Inc., Rockville Md., 2001,each of which is incorporated herein by reference.

In some embodiments, the agent includes elongated bone-derived particlesor fragments of small intestinal submucosa combined longitudinally intothree small bundles, each having, for example, from about 1 to about 3tissue particles. The three bundles may then be braided. Various methodsof braiding and types of braids any of which may be useful in producingthe covering. The ends of the braided tissue-derived particles may thenbe glued together using a fixation agent to prevent their unraveling, orthey may be held together with a biocompatible polymer or metal band.

In some embodiments, bone-derived particles are combined with a solventto form agent. Exemplary solvents include water, lower alkanols,ketones, and ethers and mixtures of any of these or other materials. Theagent may then be extruded at an appropriate temperature and pressure tocreate a thread. Threads may also be produced by spinning, drawing,rolling, solvent-extruding, cutting or laser cutting from a sheet or barstock. The agent may alternatively be cast or molded into a solid sheetor bar stock and then cut into thin threads. These may be usedimmediately or woven into a mesh. Alternatively or in addition, they maybe spliced, wrapped, plied, cabled, braided, woven, or some combinationof these. The agent may be shaped by thermal or chemical bonding, orboth. In some embodiments, a portion of the solvent is removed from theagent before extrusion.

In some embodiments, a thread of a biocompatible natural or syntheticagent, for example, polylactide or collagen, may be coated withtissue-derived or other elements, for example, by dubbing. For example,a polymer fiber may be coated with an adhesive, for example, lecithin,and bone particles or other osteoconductive or osteoinductive fibrilsallowed to adhere to the thread. The thread may then be twisted onitself or with a second or a plurality of similarly treated threads.Alternatively or in addition, the threads may be braided. The adhesivemay be a lipid that is waxy at room temperature, for example, a di- ortri-glyceride that is solid at room temperature. Alternatively or inaddition, the adhesive may be a phosphocholine or phosphatidylcholine.In some embodiments, the adhesive is a material that binds both thethread and the agent that is used to coat the thread (e.g., boneparticles) but that does not degrade either. Non-aqueous adhesives mayimprove the stability of the final aggregate as compared to aqueousadhesives.

The covering shape, mesh size, cable thickness, and other structuralcharacteristics, such as architecture, may be customized for a selectedimplant configuration, as described herein. For example, where a twodimensional aggregate is used to retain a thixotropic material within agap, a tight weave is preferred to prevent leakage. To optimize cell orfluid migration through the mesh, the pore size may be optimized for theviscosity and surface tension of the fluid or the size of the cells. Forexample, pore sizes on the order of approximately 100-200 μm may be usedif cells are to migrate through the mesh. Mesh size may be controlled byphysically weaving strands of the material by controlling the ratio ofsolvent to solids in a precursor material.

Cells may be seeded onto an agent, or contained within it. In someembodiments, cells may be encapsulated in a matrix such as alginate orcollagen gel and the capsules placed on the agent. Seeded materialsgenerally do not need to be incubated for long periods of time insolutions that could partially dissolve the binding agent. Instead, thecapsules may be placed on the agent or covering shortly beforeimplantation. In another embodiment, cells are simply mixed with a gelwhich is then combined with the agent. Alternatively, an agent orcovering may be cultured with cells before implantation. In oneembodiment, thicker materials are used for culturing to increasemechanical integrity during implantation. Any class of cells, includingconnective tissue cells, organ cells, muscle cells, nerve cells, andstem cells, may be seeded onto the spinal implant. In an exemplaryembodiment, connective tissue cells such as osteoblasts, osteoclasts,fibroblasts, tenocytes, chondrocytes, and ligament cells and partiallydifferentiated stem cells such as mesenchymal stem cells and bone marrowstromal cells are employed.

The agent may be packed in the covering at any suitable density. Forsome applications, the agent may be loosely packed in the covering toenhance manipulability. In some embodiments, the agent may be packed inthe covering such that the covering retains flexibility and may befolded over itself. In some embodiments, the covering may be configuredto facilitate placement of graft material in the covering as describedherein.

In some embodiments, the agent may be homogenous or heterogeneous. Theagent may be selected to exhibit certain gradients. For example, theagent may be selected to exhibit a gradient to guide, lure, or attractcells along a pathway. Such gradient may comprise a cell gradient, acell type gradient (for example transitioning from bone cells tocartilage cells or transitioning from bone cells to tendon cells), agradient of conductivity, or a gradient of density/porosity. In someembodiments, the agent may comprise a sequence of ingredients.

For embodiments wherein the agent is biologic, the agent may beautogenic, allogenic, xenogenic, transgenic, or combinations of these.Each of these tissue types includes any tissue of bone origin,connective tissue origin, or any collagen containing material includingorgan tissues. Other suitable agent that may be positioned in thecovering include, for example, protein, hormones, nucleic acid,carbohydrate, lipids, collagen (autograft, allograft, or xenograft frommusculoskeletal or organ systems), allograft bone, autograft bone,cartilage stimulating substances, allograft cartilage, TCP, TCP/calciumsulfate, calcium carbonate, calcium phosphates, bioactive glasses, glassceramics, magnesium phosphates, phosphates containing any biocompatiblemetal ion, porous implants of all types including trabecular metal,biocompatible metals including stainless steel, cobalt-chrome, titanium,titanium alloys, polymers such as polylactic acid, polyglycolic acid,polycaprolactone, polyglycolide-co-caprolactone, polyethylene oxide,polypropylene oxide, polyglycolide-co-trimethylene carbonate,poly(lactic-co-glycolic acid), poly-L-lactide, polyethylene glycol,polyetheretherketones, polyurethanes, polyethers of all types, polyethylene terephthalte, polyethylene, polypropylene, Teflon, chondroitinsulfate, hyaluronic acid and its salts, chitosan and derivatives,natural polymers such as silk, collagen, polysaccharides,polyhydroxyalkanoates, polymers combined with bone or collagen or bothfrom any source (allograft, xenograft, transgenic, autograft),hydroxyapatite, calcium sulfate, polymer, nanofibrous polymers, growthfactors, carriers for growth factors, growth factor extracts of tissues,demineralized bone matrix, dentine, bone marrow aspirate, bone marrowaspirate combined with various osteoinductive or osteoconductivecarriers, concentrates of lipid derived or marrow derived adult stemcells, umbilical cord derived stem cells, adult or embryonic stem cellscombined with various osteoinductive or osteoconductive carriers,transfected cell lines, bone forming cells derived from periosteum,combinations of bone stimulating and cartilage stimulating materials,committed or partially committed cells from the osteogenic orchondrogenic lineage, platelets, activated platelets, antibiotics,substances with antimicrobial properties, or combinations of any of theabove. In accordance with one embodiment, the agent is a bone matrixcomposition such as described in U.S. patent application Ser. No.12/140,044 and U.S. Patent Publications Nos. 2007/0098756 and2007/0110820 all for Bone Matrix Compositions and Methods, hereinincorporated by reference in their entireties. Suitable agent forpreparing biocomposites for placement in the covering are disclosed inU.S. Patent Publication Nos. 2007/0191963, 2006/0216323, and2005/0251267, U.S. Pat. Nos. 6,696,073, 6,478,825, 6,440,444, and6,294,187, all herein incorporated by reference in their entireties forall purposes.

In some embodiments, the spinal implant may be used in the disc space,between implants, or inside a cage. In some embodiments, the agent mayinclude a natural and/or synthetic expandable material. The expandablematerial may comprise bone particles, a polymer, a hydrogel, a sponge,collagen, or other material. In various embodiments, the expandablematerial comprises bone allograft comprising demineralized boneparticles, and the demineralized bone particles may be a blend ofcortical and cancellous bone. For example, the expandable material maycomprise demineralized cortical fibers and demineralized cancellouschips, wherein the demineralized cancellous chips may create a healthymatrix for the incorporation of new bone and add advanced expansioncharacteristics.

In addition to bone particles, an expandable polymer, a collagen sponge,compressed and/or dried hydrogels, or other materials may be used. Inaddition to expansion properties, the agent may exhibit osteoinductiveand/or osteoconductive properties. For example, cancellous boneparticles may exhibit osteoconductive properties while demineralizedcortical bone particles may exhibit osteoinductive properties.

In some embodiments, the agent may be supplemented, further treated, orchemically modified with one or more bioactive agents or bioactivecompounds. Bioactive agent or bioactive compound, as used herein, refersto a compound or entity that alters, inhibits, activates, or otherwiseaffects biological or chemical events. For example, bioactive agents mayinclude, but are not limited to, osteogenic or chondrogenic proteins orpeptides; demineralized bone powder; collagen, insoluble collagenderivatives, etc., and soluble solids and/or liquids dissolved therein;anti-AIDS substances; anti-cancer substances; antimicrobials and/orantibiotics such as erythromycin, bacitracin, neomycin, penicillin,polymycin B, tetracyclines, biomycin, chloromycetin, and streptomycins,cefazolin, ampicillin, azactam, tobramycin, clindamycin and gentamycin;bacteriaphages; immunosuppressants; anti-viral substances such assubstances effective against hepatitis; enzyme inhibitors; hormones;neurotoxins; opioids; hypnotics; anti-histamines; lubricants;tranquilizers; anti-convulsants; muscle relaxants and anti-Parkinsonsubstances; anti-spasmodics and muscle contractants including channelblockers; miotics and anti-cholinergics; anti-glaucoma compounds;anti-parasite and/or anti-protozoal compounds; modulators ofcell-extracellular matrix interactions including cell growth inhibitorsand antiadhesion molecules; vasodilating agents; inhibitors of DNA, RNA,or protein synthesis; anti-hypertensives; analgesics; anti-pyretics;steroidal and non-steroidal anti-inflammatory agents; anti-angiogenicfactors; angiogenic factors and polymeric carriers containing suchfactors; anti-secretory factors; anticoagulants and/or antithromboticagents; local anesthetics; ophthalmics; prostaglandins;anti-depressants; anti-psychotic substances; anti-emetics; imagingagents; biocidal/biostatic sugars such as dextran, glucose, etc.; aminoacids; peptides; vitamins; inorganic elements; co-factors for proteinsynthesis; endocrine tissue or tissue fragments; synthesizers; enzymessuch as alkaline phosphatase, collagenase, peptidases, oxidases, etc.;polymer cell scaffolds with parenchymal cells; collagen lattices;antigenic agents; cytoskeletal agents; cartilage fragments; living cellssuch as chondrocytes, bone marrow cells, mesenchymal stem cells; naturalextracts; genetically engineered living cells or otherwise modifiedliving cells; expanded or cultured cells; DNA delivered by plasmid,viral vectors, or other means; tissue transplants; autogenous tissuessuch as blood, serum, soft tissue, bone marrow, etc.; bioadhesives; bonemorphogenic proteins (BMPs); osteoinductive factor (IFO); fibronectin(FN); endothelial cell growth factor (ECGF); vascular endothelial growthfactor (VEGF); cementum attachment extracts (CAE); ketanserin; humangrowth hormone (HGH); animal growth hormones; epidermal growth factor(EGF); interleukins, e.g., interleukin-1 (IL-1), interleukin-2 (IL-2);human alpha thrombin; transforming growth factor (TGF-beta);insulin-like growth factors (IGF-1, IGF-2); parathyroid hormone (PTH);platelet derived growth factors (PDGF); fibroblast growth factors (FGF,BFGF, etc.); periodontal ligament chemotactic factor (PDLGF); enamelmatrix proteins; growth and differentiation factors (GDF); hedgehogfamily of proteins; protein receptor molecules; small peptides derivedfrom growth factors above; bone promoters; cytokines; somatotropin; bonedigesters; antitumor agents; cellular attractants and attachment agents;immuno-suppressants; permeation enhancers, e.g., fatty acid esters suchas laureate, myristate and stearate monoesters of polyethylene glycol,enamine derivatives, alpha-keto aldehydes, etc.; and nucleic acids.

In some embodiments, the bioactive agent may be a drug. In someembodiments, the bioactive agent may be a growth factor, cytokine,extracellular matrix molecule, or a fragment or derivative thereof, forexample, a protein or peptide sequence such as RGD. A more completelisting of bioactive agents and specific drugs suitable for use in thepresent invention may be found in “Pharmaceutical Substances: Syntheses,Patents, Applications” by Axel Kleemann and Jurgen Engel, Thieme MedicalPublishing, 1999; the “Merck Index: An Encyclopedia of Chemicals, Drugs,and Biologicals”, Edited by Susan Budavari et al., CRC Press, 1996; andthe United States Pharmacopeia-25/National Formulary-20, published bythe United States Pharmacopeia Convention, Inc., Rockville Md., 2001.

In some embodiments, the drug can be a statin. Examples of a usefulstatin for treatment of pain and/or inflammation include, but is notlimited to, atorvastatin, simvastatin, pravastatin, cerivastatin,mevastatin, velostatin, fluvastatin, lovastatin, rosuvastatin andfluindostatin (Sandoz XU-62-320), dalvastain, eptastatin, pitavastatin,or pharmaceutically acceptable salts thereof or a combination thereof.In various embodiments, the statin may comprise mixtures of (+)R and(−)-S enantiomers of the statin. In various embodiments, the statin maycomprise a 1:1 racemic mixture of the statin. Anti-inflammatory agentsalso include those with anti-inflammatory properties, such as, forexample, amitriptyline, carbamazepine, gabapentin, pregabalin,clonidine, or a combination thereof.

Sheet 12 includes a side 22. Side 22 includes a surface 24, which isconfigured for connection with surface 16 via connectable surfaces, asdescribed herein. In some embodiments, the connectable surfaces includea hook configuration 26 disposed with surface 24 and a loopconfiguration 28 disposed with surface 16 to facilitate connection ofsurfaces 16, 24. In some embodiments, hook and loop configuration 26, 28comprise Velcro. In some embodiments, the foldable walls of sheet 12include a plurality of panels 30, 30 a and 30 b that are folded upon oneanother such that the covering can be folded into spinal implant 11 in aselected implant configuration. Panels 30 are connected by delineations,such as, for example, fold lines 32.

Surface 24 is connected with surface 16 via connectable surfacesintra-operatively forming a selected implant configuration, as describedherein. In some embodiments, sheet 12 is folded to form the selectedimplant configuration. In some embodiments, the selected implantconfiguration includes a specific cross section. In some embodiments,the cross section can include, for example, tubular, cylindrical,circular, oval, rectangular and/or square.

In some embodiments, the selected implant configuration has a crosssectional shape selected from generally circular or generally oval and ashape that can be tubular, rectangular, or cubic. In some embodiments,the selected implant configuration of the covering may include anexpanded configuration. In some embodiments, expansion can be providedsuch that the covering expands when placed in the body or the coveringmay be made of a material that expands when it comes in contact withwater or other bodily fluids, either by way of liquid absorption, or bystretching when the materials absorb liquid and expand. In someembodiments, the covering may be substantially non-expandable orminimally deformable.

In some embodiments, the selected implant configuration of spinalimplant 11 can include, for example, a cylinder or a bag, whether thecovering has a single or a plurality of compartments, and whether thecovering includes attachment mechanisms. In some embodiments, theselected implant configuration of spinal implant 11 may be configured toconform to surrounding bony contours of the space in which it is placed.

In some embodiments, the selected implant configuration of spinalimplant 11 can include a ring, a cylinder, a cage, a rectangular shape,a mesh, a suture-like wrap, a continuous tube, or other configuration.In some embodiments, the selected implant configuration of spinalimplant 11 is designed to fit adjacent to spinal processes forposterolateral spine fusion, a cube like structure designed to fitbetween vertebral bodies or within cages for interbody spinal fusion, atube-like shape where the ends are designed to be fitted onto nonunionlong bone defects, relatively flat shapes designed to fill cranial ormaxillofacial defects, rectangular structures designed for osteochondraldefects, structures shaped to fit around various implants (for example,dental, doughnut with hole for dental implants), or relatively elasticring-like structures that will stretch and then conform to shapes (forexample, rubber band fitted around processes). In some embodiments, theselected implant configuration of spinal implant 11 includes a cage,which comprises a plurality of compartments. For example, in a tubularembodiment, the tube may be formed into a plurality of compartments bytying a cord around the tube at one or more points, or by other suitablemechanism such as crimping, twisting, knotting, stapling, sewing, orother. The selected implant configuration of the covering may bedetermined by the agent to be provided within the covering. For example,if the agent to be contained comprises fibers, the covering may beformed as strings or sutures that are wrapped around the fibers.

In some embodiments, surfaces 16, 24 can be connected by connectablesurfaces, such as, for example, a draw string, stitches, sutures, heatseals, adhesion, pressure fittings, coil ring, twist tie or combinationsthereof. In some embodiments, the connectable surfaces can be defined byportions of sheet 12, such that manipulation, such as, for example, byfolding, bending and/or twisting of sheet 12 forms a closed container inthe selected implant configuration.

In some embodiments, agent 20 is disposed with surface 16. Sheet 12 ismanipulated intra-operatively, such as, for example, by folding. Sheet12 is folded such that panel 30 is pivoted and/or rotated, in adirection shown by arrow A in FIG. 2. Sheet 12 is folded such that panel30 b is pivoted and/or rotated, in a direction shown by arrow B in FIG.2. Panel 30 is folded such that a portion of surface 24 disposed withpanel 30 is adjacent and facing a portion of surface 16 disposed withpanel 30 b. Folding of panels 30, 30 b facilitates engagement andfixation of surfaces 16, 24 to dispose the foldable walls of thecovering in a selected implant configuration of spinal implant 11.

As panels 30, 30 b are manipulated, surface 24 is connectable withsurface 16 to fix panels 30, 30 a, 30 b in the selected configuration,as shown in FIG. 4. In some embodiments, surface 24 can be disengagedfrom surface 16 to facilitate reconfiguration and/or adjustment ofpanels 30, 30 a, 30 b into a new or second revised selectedconfiguration such that the selected configuration is customizableintra-operatively. Upon folding of panels 30, 30 b, agent 20 is encasedand/or contained by panels 30, 30 a, 30 b to retain agent 20 therein.Panels 30, 30 a, 30 b are manipulated to enclose end portions of theselected configuration.

In use, spinal implant system 10, similar to the systems and methodsdescribed herein, is employed to treat a selected section of vertebraeV. In some embodiments, spinal implant 11 is employed with vertebrae Vat the surgical site during a surgical procedure, such as, for example,a posterolateral fusion, as shown in FIG. 5. A medical practitionerobtains access to a surgical site including vertebrae V in anyappropriate manner, such as through incision and retraction of tissues.In some embodiments, spinal implant system 10 can be used in anyexisting surgical method or technique including open surgery, mini-opensurgery, minimally invasive surgery and percutaneous surgicalimplantation, whereby vertebrae V is accessed through a mini-incision,or sleeve that provides a protected passageway to the area. Once accessto the surgical site is obtained, the particular surgical procedure canbe performed for treating a spine disorder.

An incision is made in the body of a patient and a cutting instrument(not shown) creates a surgical pathway for implantation of components ofspinal implant system 10 with a portion of vertebrae V including one ormore transverse process TP. A preparation instrument (not shown) can beemployed to prepare tissue surfaces of vertebrae V.

In some embodiments, sheet 12 and agent 20 are selected based on one ormore parameters, such as, for example, patient anatomy, patientdisorder, surgical procedure, surgical conditions, intra-operativeconditions, modification or strategy and/or practitioner preference.Based on the one or more parameters, sheet 12 includes a firstconfiguration and is manipulated and/or folded into a selected implantconfiguration intra-operatively to contain agent 20 and comprise spinalimplant 11.

Sheet 12 is disposed in a substantially flat or even configuration, asshown in FIG. 1. Agent 20 is disposed with surface 16, as describedherein. Sheet 12 is manipulated intra-operatively. Sheet 12 is foldedsuch that panel 30 is pivoted and/or rotated, in a direction shown byarrow A in FIG. 2. Sheet 12 is folded such that panel 30 b is pivotedand/or rotated, in a direction shown by arrow B in FIG. 2. Panel 30 isfolded such that a portion of surface 24 disposed with panel 30 isadjacent and facing a portion of surface 16 disposed with panel 30 b, asshown in FIG. 3. Folding of panels 30, 30 b facilitates engagement andfixation of the connectable surfaces of surfaces 16, 24, as describedherein, to dispose the foldable walls of the covering in a selectedimplant configuration of spinal implant 11. As panels 30, 30 b aremanipulated, surface 24 is connectable with surface 16 to fix panels 30,30 a, 30 b in the selected configuration, as shown in FIG. 4. Uponfolding of panels 30, 30 b, agent 20 is encased and/or contained bypanels 30, 30 a, 30 b to retain agent 20 therein. Panels 30, 30 a, 30 bare manipulated to enclose end portions of the selected configuration ofspinal implant 11.

In the selected implant configuration, as shown in FIG. 5, spinalimplant 11 is disposed in a selected orientation with the one or moretransverse process TP and/or adjacent portions of vertebrae V at thesurgical site in connection with the posterolateral fusion.

In some embodiments, sheet 12 may contain an attachment or couplingmechanism, as described herein, to attach spinal implant 11 to skeletalor soft tissue proximate to a surgical site. In some embodiments, theattachment mechanism can include a tab, loop, tack or a hook-and loop(Velcro) portion.

In some embodiments, the attachment mechanisms may provide forattachment to other coverings, or for attachment to adjacent implantablemedical devices or products (such as a rod or screw or cross-brace of apedicle screw fixation system, a hip prosthesis, a bone plate, and thelike). In some embodiments, the attachment mechanisms may provide forattachment to bone or to adjacent tissues such as muscle, tendon, orligament. Chemical attachment mechanisms may comprise, for example, abioadhesive or glue, cement, tape, tissue adhesives, or similarmechanism. Chemical attachment mechanisms may further comprisemechanisms that facilitate cross-linking. In some embodiments,attachment mechanisms such as crimping, welding, soldering, or brazingmay be used. Further, attachment may be achieved via friction. In someembodiments, biological attachment may be via mechanisms that promotetissue ingrowth such as by a porous coating or ahydroxyapatite-tricalcium phosphate (HA/TCP) coating.

In some embodiments, spinal implant system 10 comprises a kit includinga plurality of alternate implants 11, similar to that described herein.In some embodiments, spinal implant system 10 can include one or aplurality of fasteners such as those described herein and/or fixationelements, which may be employed with a single vertebral level or aplurality of vertebral levels. In some embodiments, the fasteners may beengaged with vertebrae in various orientations, such as, for example,series, parallel, offset, staggered and/or alternate vertebral levels.In some embodiments, the fasteners may be configured as multi-axialscrews, sagittal angulation screws, pedicle screws, mono-axial screws,uni-planar screws, fixed screws, anchors, tissue penetrating screws,conventional screws, expanding screws. In some embodiments, thefasteners may be employed with wedges, anchors, buttons, clips, snaps,friction fittings, compressive fittings, expanding rivets, staples,nails, adhesives, posts, connectors, fixation plates and/or posts.

It will be apparent to those skilled in the art that variousmodifications and variations can be made to various embodimentsdescribed herein without departing from the spirit or scope of theteachings herein. Thus, it is intended that various embodiments coverother modifications and variations of various embodiments within thescope of the present teachings.

What is claimed is:
 1. A method for treating a spine, the methodcomprising the steps of: disposing an agent with a covering thatincludes a first surface and a second surface; the covering comprising afirst panel having an outer face formed from the second surface, asecond panel, and a third panel having an inner face formed from thefirst surface; intra-operatively folding the covering such that theouter face of the first panel is connected with the inner face of thethird panel in a selected implant configuration; and connecting theselected implant configuration with tissue, wherein the coveringcomprises a biodegradable polymer.
 2. A method as recited in claim 1,wherein the tissue includes at least one transverse process of a spine.3. A method as recited in claim 1, wherein the first surface is coveredby loops and the second surface is covered by hooks.
 4. A method asrecited in claim 1, wherein the covering is foldable between a flatconfiguration and a selected implant configuration.
 5. A method asrecited in claim 1, wherein a first side of the covering has the firstsurface to dispose the agent thereon and a second side of the coveringhas the second surface.
 6. A method as recited in claim 1, wherein thefirst, the second and the third panels are connected by fold lines.
 7. Amethod as recited in claim 1, wherein the covering comprises a porousmesh.
 8. A method as recited in claim 1, wherein the first and thesecond surfaces are connectable via a hook and loop configuration.
 9. Amethod as recited in claim 1, wherein the selected implant configurationof the covering includes a cross sectional shape selected from generallycircular or generally oval.
 10. A method as recited in claim 1, whereinthe selected implant configuration of the covering includes a shapeselected from tubular, rectangular, cube or mesh bag.
 11. A method asrecited in claim 1, wherein the agent comprises autograft or allograft.12. A method as recited in claim 1, wherein the agent comprisesdemineralized bone matrix comprising particles and fibers ofdemineralized bone.
 13. A method as recited in claim 1, wherein theagent comprises demineralized bone matrix fibers and demineralized bonematrix particles in a 30:70 ratio.
 14. A method as recited in claim 1,wherein the agent comprises bone morphogenetic protein.
 15. A method fortreating a spine, the method comprising the steps of: disposing an agentincluding autograft with a foldable polymer mesh sheet that includes afirst surface and a second surface, the foldable polymer mesh sheetcomprising a first panel having an outer face formed from the secondsurface, a second panel, and a third panel having an inner face formedfrom the first surface; intra-operatively folding the foldable polymermesh sheet such that the outer face of the first panel is connected withthe inner face of the third panel in a selected implant configuration;and connecting the selected implant configuration with tissue.
 16. Amethod as recited in claim 15, wherein the foldable polymer mesh sheetis configured to form a folded configuration such that the agent iscontained completely within the spinal implant.